This application brings together a strong interdisciplinary team of scientists at the UCSF Center for Obesity Assessment, Study and Treatment (COAST) with researchers at Kaiser-Permanente to test novel interventions based on the physiology by which stress and reward from palatable food influence eating behaviors and abdominal fat deposition. This type of eating is typically non-homeostatic (not meeting caloric deficit). We plan to reduce this type of intake through proof-of-concept and intervention strategies tailored for obese lower income women prior to pregnancy, a critical period for intervention, which may affect gestational weight gain, postpartum weight retention, and offspring weight. Our translational approach draws from the psychology of eating and behavior change, and neuroscience of stress, appetite and reward, to test whether modulating the reward and stress response systems reduces abdominal obesity and weight. In Phase 1 & 2, we will develop and compare two distinct interventions that target diet, activity, and stress but with different conceptual bases: (1): Developmental Skills Training (DST) designed to curb addictions through promoting self-regulation of emotions and eating behavior. (2); Mindfulness and Diet (MIND) aimed to reduce stress and improve awareness of hunger-satiety cues and automatic eating patterns through mindfulness and mindful eating. Preliminary data on each intervention are promising. We will also test an indirect measure of endogenous opioid tone that may provide insight into mechanisms of weight loss. Pilot research has shown that response to a naltrexone opioid probe is linked to indices of non-homeostatic eating and predicts weight loss. We will test the utility of this opioid probe to determine if it changes during treatment and predicts change in eating and abdominal fat. In Phase 2, we will randomize 80 obese women intending to become pregnant to a 3 month proof-of-concept trial of DST and MIND, to compare relative effects on proposed mechanisms (stress, opioid tone), and feasibility. In Phase 3, we will refine and test the efficacy of the most successful intervention then randomize 120 pre-pregnant obese women to the selected intervention or active control condition (diet and exercise alone). These efforts will produce promising intervention strategies for curbing obesity in women during their reproductive years. All phases will be informed by input from a Scientific Advisory panel and Data Safety and Monitoring Board. Accomplishing the aims of this proposal will expand current understanding of the mechanisms that lead to sustained weight reduction, and will inform further study of alternative strategies for obesity intervention. RELEVANCE: The proposed research develops new obesity interventions based on the science of how stress influences the rewarding value of food, and promotes compulsive eating. We will test promising interventions, with women intending to become pregnant that will result in a new prevention programs that are more effective for sustained weight loss maintenance than what is currently available. This program could have a broad public health impact by improving maternal heath and potentially benefiting the next generation. (End of Abstract)